Oral administration of tipranavir with long-chain triglyceride results in moderate intestinal lymph targeting but no efficient delivery to HIV-1 reservoir in mesenteric lymph nodes

The results showed similar oral bioavailability of TPV with and without co-administration of long-chain triglyceride vehicle

Yenju Chu; Chaolong Qin; Wanshan Feng; Charles Sheriston; Yu Jane Khor; ConcepciĆ³n Medrano-Padial; Birgit E. Watson; Teddy Chan; Binhua Ling; Michael J. Stocks; Peter M. Fischer; Pavel Gershkovich

2021

Scholarcy highlights

  • The introduction of combination antiretroviral therapy led to substantial improvement in mortality and morbidity of HIV-1 infection
  • The poor penetration of antiretroviral agents to HIV-1 reservoirs limit the ability of the antiretroviral agents to eliminate the virus
  • Intestinal lymphatic absorption pathway substantially increases the concentration of lipophilic drugs in mesenteric lymph and Mesenteric lymph nodes when they are co-administered with long-chain triglyceride
  • Lipophilic antiretroviral drugs could potentially be delivered to HIV-1 reservoirs in MLNs by LCT-based formulation approach
  • The results showed similar oral bioavailability of TPV with and without co-administration of LCT vehicle
  • LCT-based formulation led to 3-fold higher concentrations of TPV in mesenteric lymph compared to plasma, the levels of the drug in MLNs were similar to plasma in both LCT-based and lipid-free formulation groups
  • long-chain triglyceride-based formulation approach alone was not sufficient for effective delivery of TPV to Mesenteric lymph nodes. Future efforts should be directed to a combined highly lipophilic prodrugs/lipid-based formulation approach to target TPV, other protease inhibitors and potentially other classes of antiretroviral agents to viral reservoirs within the mesenteric lymphatic system

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